Development and Temporal Validation of a Three-Metabolite Cerebrospinal Fluid Model for the Diagnosis of Leptomeningeal Metastasis from Solid Tumors

Background/Objectives: Leptomeningeal metastasis (LM) is a severe complication of solid tumors. Cerebrospinal fluid (CSF) cytology is only about 70% sensitive on a single examination, and objective markers are needed.

Methods

CSF from 49 patients with LM and 16 with intracranial disease without LM was analyzed by targeted LC–MS in a training batch (n = 30) and a temporally independent validation batch (n = 35). Metabolites selected by both LASSO and random forest entered a logistic regression model, which was applied unchanged to the validation batch and evaluated by repeated and nested cross-validation on all 65 samples.